The Spanish Pancreatic Club recommendations for the diagnosis and treatment of chronic pancreatitis: part 1 (diagnosis).

Chronic pancreatitis (CP) is a relatively uncommon, complex and heterogeneous disease. The absence of a gold standard applicable to the initial phases of CP makes its early diagnosis difficult. Some of its complications, particularly chronic pain, can be difficult to manage. There is much variability in the diagnosis and treatment of CP and its complications amongst centers and professionals. The Spanish Pancreatic Club has developed a consensus on the management of CP. Two coordinators chose a multidisciplinary panel of 24 experts on this disease. A list of questions was drafted, and two experts reviewed each question. Then, a draft was produced and shared with the entire panel of experts and discussed in a face-to-face meeting. This first part of the consensus addresses the diagnosis of CP and its complications.

The Spanish Pancreatic Club's recommendations for the diagnosis and treatment of chronic pancreatitis: part 2 (treatment).

Chronic pancreatitis (CP) is a complex disease with a wide range of clinical manifestations. This range comprises from asymptomatic patients to patients with disabling symptoms or complications. The management of CP is frequently different between geographic areas and even medical centers. This is due to the paucity of high quality studies and clinical practice guidelines regarding its diagnosis and treatment. The aim of the Spanish Pancreatic Club was to give current evidence-based recommendations for the management of CP. Two coordinators chose a multidisciplinary panel of 24 experts on this disease. These experts were selected according to clinical and research experience in CP. A list of questions was made and two experts reviewed each question. A draft was later produced and discussed with the entire panel of experts in a face-to-face meeting. The level of evidence was based on the ratings given by the Oxford Centre for Evidence-Based Medicine. In the second part of the consensus, recommendations were given regarding the management of pain, pseudocysts, duodenal and biliary stenosis, pancreatic fistula and ascites, left portal hypertension, diabetes mellitus, exocrine pancreatic insufficiency, and nutritional support in CP.

[Autoimmune pancreatitis: inflammatory pseudotumor, multifocal fibrosclerosis, portal hypertension, and long-term outcome]. / Pancreatitis autoinmune: pseudotumor inflamatorio, afectación multifocal, hipertensión portal y evolución a largo plazo.

Autoimmune pancreatitis is a recently characterized disease that still constitutes a diagnostic challenge, especially regarding differential diagnosis from neoplasia. Long-term outcome is poorly known. We herein report a case of a patient with autoimmune pancreatitis and 14 years of follow-up, and show its clinical, biochemical, and morphological characteristics. A 54-year-old female presented with obstructive jaundice and abdominal tenderness, as well as a mass at the pancreatic head on a CT scan, suggestive of pancreatic neoplasia. Surgery showed an increase of the whole pancreas, malignancy was intraoperatively ruled out, and a cholecystectomy and choledochoduodenostomy were carried out. The diagnosis was chronic pancreatitis. Over the following years different autoimmune complications developed, including asthma, salivary gland swelling, and sclerosing cholangitis, as well as recurrent episodes of jaundice, and exocrine and endocrine pancreatic failure. The development of these complications combined with the demonstration of high serum levels of IgG4 and carbonic anhydrase II led to a re-evaluation of the initial histology of the pancreas, leading to a final diagnosis of autoimmune pancreatitis: IgG4+ lymphoplasmacytic infiltrates, fibrosis, and obliterative phlebitis. New complications developed during the last few years: retroperitoneal fibrosis with portal hypertension, esophageal varices, and splenomegaly.

Effect of L-carnitine upon ammonia tolerance test in cirrhotic patients.

In a group of liver cirrhosis (LC) patients subjected to a rectal ammonium overload test, the effect of L-carnitine on ammoniemia and on the type A numerical connection and star clock psychomotor tests has been evaluated. On comparing 40 LC patients given L-carnitine with 40 control cirrhotics given a placebo, no significant differences were observed in ammonium levels after performing the overload test in both groups. However, on studying the patients with the greatest liver involvement, those given L-carnitine showed smaller elevations in ammoniemia and better responses to the psychometric tests than those receiving the placebo. The results obtained emphasize the need to continue testing the effect of L-carnitine using either similar tests or carrying out long-term evaluations to determine its protective effect in the appearance of hepatic encephalopathy, perhaps even including its evaluation in the treatment of established encephalopathy.

Acute necrotizing pancreatitis: a multicenter study.

A multicenter study of acute necrotizing pancreatitis (ANP) classified in accordance with the Balthazar criteria (grades D and E), has been performed in 12 teaching hospitals. A total of 233 patients were reviewed, and the mortality rate was 26.6%. The most common etiology was biliary pancreatitis (45.5%). Among the complications, shock, renal insufficiency, pulmonary insufficiency and hemorrhagic gastritis were associated with a mortality rate of 51-66%. Diffuse fluid collections were associated with a higher mortality rate (26.8%) than localized fluid collections (14.5%). In 106 patients with gallstone pancreatitis, early surgery was performed in 17, and 5 patients (29.4%) died. No mortality was observed in 32 patients with delayed surgery. Sphincterotomy was performed in 13 patients, and 4 (30.7%) died. Early surgery (necrosectomy and closed peritoneal lavage) was undertaken in 75 patients, with a mortality rate of 39%. In conclusion, the morbidity and mortality rates of ANP can be improved with proper monitoring, adequate supportive care and the judicious use of surgery based on clinical and morphological findings.

Plasma sulfobromophthalein disappearance in Gilbert's syndrome.

BACKGROUND/AIMS: We studied the metabolism of sulfobromophthalein and its relationship with serum bilirubin levels in 40 patients with Gilbert's syndrome (type I 30; type II 6; type III 4). MATERIAL AND METHODS: Plasma sulfobromophthalein disappearance studies were carried out and 72 hours later, serum bilirubin concentrations (total and unconjugated fraction) were determined at baseline and after 24 and 48 hours of dietary restriction to 400 calories/day. RESULTS: The fractional transfer rate of sulfobromophthalein from plasma to liver was significantly higher in types I (14.7 +/- 3.4 ml/min) and II (14.9 +/- 2.7 ml/min) than in type III (8.7 +/- 1.5 ml/min). The fraction of the plasma sulfobromophthalein pool irreversibly cleared per min was significantly higher in type I (12.2 +/- 2.6 ml/min) than in types II (9.5 +/- 1.5 ml/min) and III (9.3 +/- 3.8). In all patients, serum bilirubin concentrations were significantly higher after fasting as compared with baseline. There was a significant correlation between the increments of serum unconjugated bilirubin levels after the fasting test and the transfer rate of sulfobromophthalein from plasma to liver (F = 9.8411, r = -0.4535, p = 0.003). CONCLUSION: These findings indicate the presence of an active uptake system shared by bilirubin and sulfobromophthalein.

[Prevalence of malnutrition and morphofunctional alterations of the pancreas in asymptomatic chronic alcoholic patients]. / Prevalencia de la disfunción pancreática y de la desnutrición en pacientes alcohólicos en programa de deshabituación.

BACKGROUND: The aim of this study was to assess the prevalence of morphofunctional alterations of the pancreas and the possible association with the nutritional status of chronic alcoholic subjects in the initial phase of detoxification and without symptoms of pancreopathy. PATIENTS AND METHODS: 105 alcoholic patients with neither diagnosis nor clinical symptoms of pancreopathy were studied, from detoxification units for alcoholics with over 30 days abstinence. The nutritional status was evaluated by means of clinico-anthropometric parameters (body mass index, nutritional risk index, degree and type of malnutrition) and biological parameters (albumin, transferrin, and total lymphocyte count). The pancreas was morphologically examined by means of plain X-rays, ultrasonography and/or computer tomography, applying the Cambridge criteria; also functionally (Pancreolauryl test and fats in stools). RESULTS: The average (SD) consumption of alcohol was 195 (76) g/day (range 60-450), for 16 (8) years (3-40). Nutritional abnormalities were observed between 12.3% and 28% in the clinico-anthropometric parameters, and between 2% and 32% according to the biological parameters. These abnormalities were only light or moderate. The morphologic study showed abnormalities in 3.5% of the cases. Abnormalities in the exocrine function were observed in 26% of the cases, of which one third showed steathorrhea. A significant association between the nutritional condition and the scores of the tests of exocrine function was observed, especially in those cases with steathorrea. CONCLUSION: A large number of asymptomatic alcoholic subjects present a subclinical pancreopathy and signs of malnutrition. Both facts may be related and justify a pancreatic examination with more sensitive techniques in alcoholic individuals with malnutrition.

Maximal biliary transport of sulfobromophthalein in patients with a T-tube placed in the common bile duct.

In 19 adult patients with choledocholithiasis who were operated on, excretion of free and conjugated sulfobromophthalein (BSP) in the bile collected through a T-tube inserted in the common bile duct was determined. The transport maximum (Tm) for BSP was calculated by the constant-infusion technique after an intravenous infusion of the dye at a rate of 0.3 and 0.09 mg/kg/min for the first and second hour, respectively. Free and conjugated BSP were measured in blood samples obtained at 30, 40, and 50 min of each hourly-infusion period, and in bile collected during the first 30 min (sample A) and between 30-50 min (sample B) after starting the first BSP infusion, and during the first 30 min (sample C) and between 30-50 min (sample D) after starting the second infusion. No correlations between Tm of BSP and glutathione transferase activity and between Tm and bilirubin and alkaline phosphatase in serum were found. Although there was an overall correlation between Tm of BSP and biliary excretion of BSP after 30 min of starting the BSP infusion (samples B, C and D) (r = 0.4716; P = 0.41), Tm values were always lower than recoveries of free BSP in bile. It seems that Tm of BSP (measured with the Wheeler's method) overestimates the actual values of biliary excretion of free BSP, and that the percentage of conjugated BSP in serum is related to the degree of impairment of biliary transport of BSP.

Influence of alcohol consumption on the initial development of chronic pancreatitis.

The aim of our study was to analyze the influence of alcohol consumption on the early clinical manifestations of alcoholic chronic pancreatitis of the 517 patients in whom chronic pancreatitis was initially suspected, 158 were diagnosed with this disease; of these, alcohol was considered the cause in 136 (86.1%). Alcohol was considered a major etiologic factor when mean consumption was > or = 60 grams per day for at least 4 years. Alcohol consumption, initial clinical manifestations and time of onset were considered up until the moment of diagnosis in all patients. The sex distribution was 133 men (97.8%) and 3 women (2.2%). The average age was 22 +/- 6.5 years at onset of alcoholism, 38 +/- 9.4 years at onset of clinical features, and 44 +/- 9.4 years at diagnosis. The interval between the onset of alcoholism and the initial clinical manifestations was 15.8 +/- 8.8 years, and the interval between the latter and diagnosis was 6.1 +/- 4.9 years. Average alcohol consumption was 162 +/- 8 grams/day and total consumption was 1312 +/- 1017 kg. A statistically significant relationship was found only for mean alcohol consumption and abdominal pain. We found a higher frequency of acute pancreatitis outbreaks, calcifications, steatorrhea and diabetes until the moment of diagnosis in the higher alcohol consumption groups, although the relationship was not statistically significant.

Diagnosis of chronic pancreatitis: presenting features and diagnostic delay.

The diagnosis of chronic pancreatitis continues to present difficulties. The nonspecific nature of the symptomatology, its low prevalence and the limited value of morphological and functional tests in the early stages are the most common causes of delay in diagnosis. Our aim was to analyze the most significant clinical manifestations and the diagnostic features of chronic pancreatitis, distinguishing between alcoholic and nonalcoholic etiologies. We studied 158 patients, 136 (86.1%) with alcoholic and 22 (13.9%) with nonalcoholic chronic pancreatitis. The initial symptomatology, the age at diagnosis, the delay in diagnosis from the onset of the clinical signs and the type of diagnosis (incidental or suspected) were considered for each patient. Men predominated in both the alcoholic and the nonalcoholic pancreatitis groups (97.8% and 68.2%, respectively). The mean ages at onset and diagnosis were 38 and 50.6 years, respectively, in alcoholic chronic pancreatitis and 44 and 55 years in the nonalcoholic group; the differences between the two parameters were statistically significant. The most common clinical signs in alcoholic chronic pancreatitis were abdominal pain (81.6%) and episodes of acute pancreatitis (64%), while patients with nonalcoholic pancreatitis presented abdominal pain (59%), diarrhea (40.9%) and weight loss (36.4%). The delay in diagnosis from the onset of the clinical manifestations was 5.8 years (6.1 years in alcoholic and 4.3 years in nonalcoholic pancreatitis. The diagnosis was incidental in 34% of cases of alcoholic chronic pancreatitis and in 50% of cases in the nonalcoholic group.

[Biliary drainage in the diagnosis of microlithiasis. Value in acute idiopathic pancreatitis and in persistent pain in the right hypochondrium]. / El drenaje biliar en el diagnóstico de la microlitiasis. Valor en la pancreatitis aguda idiopática y en el dolor en hipocondrio derecho persistente.

We present a microscopic study of bills obtained via biliary drainage from 33 patients with the diagnosis of acute idiopathic pancreatitis, 33 subjects with pain in the epigastrium and U.Q. with the suspicion of biliary origin, but not revealed by means of routine techniques, and 14 patients with confirmed biliary lithiasis. Duodenal intubation under radiological control was used in all cases, with the administration of 2 UI/kg of CCK IV, in order to study bile A and B under polarized light microscopy. We found cholesterol crystals in 12 cases (36.3%) of acute idiopathic pancreatitis, 5 cases (15.1%) of right hypocondrial pain, and 14 (100%) of biliary lithiasis. Calcium bilirubinate granules were obtained in 15 cases (45.4%) of acute idiopathic pancreatitis, 8 cases (24.4%) of pain in the right hypocondrium and 7 (50%) of biliary lithiasis. We detected giardia in one case of acute idiopathic pancreatitis and an other with pain in the right U.Q. In conclusion, biliary drainage reveals its diagnostic importance in the study of biliary pathology in patients diagnosed of acute idiopathic pancreatitis as well as in cases of chronic right U.Q. al pain suggestive of biliary pathology.

[Hepatic activity of glutathione transferase and bromsulphalein metabolism]. / Actividad hepática de la glutatión transferasa y metabolismo de la bromosulfotaleína.

The gluthatione transferase activity has been studied in liver biopsies from patients suffering with different hepatic lesion and related to the bromsulphalein (BSP) maximal transport (MT) and the conjugated dye present in serum. Results prove that the MT of BSP is independent of the enzyme activity, but is correlated to the conjugated BSP present in serum during the first perfusion. The enzyme activity, the MT of BSP and BSP conjugated rare in serum are not related to the liver lesion stage. From the analysis of our results we conclude that in the beginning the BSP conjugated proportion is determined by the enzyme activity which is not a restrictive factor of the BSP maximal transport.

[A comparative study of the oral and rectal ammonium overload test in liver cirrhosis]. / Estudio comparativo del test de sobrecarga amónica por vía oral y rectal en la cirrosis hepática.

The ammonium loading test has been realized in 66 patients, 8 of them without clinical or laboratory data of hepatic disease and 58 diagnosed of hepatic cirrhosis (HC). In 40 patients with HC and 8 patients without liver disease the ammonium was administered by rectum and in the remaining 18 patients with HC it was administrated orally. In each case, non stagnant venous blood was drawn at 0, 30, 45, 60 and 75 minutes after the administration of ammonium and plasmatic levels were measured. The results show that in patients with HC there are no significant differences between rectal and oral administration although the rectal way presented less secondary effects and is better tolerated. The test is discriminatory when comparing patients with HC and patients without liver disease as well as between patients with HC and portal hypertension and those without clinical signs of portal hypertension.

[Recurrent benign intrahepatic cholestasis. A case report]. / Colestasis intrahepática recurrente benigna. A propósito de un caso.

A case of benign and recurrent intrahepatic cholestasis in a 46 year old female is presented. This patient, who correctly coincided with the diagnosis criteria, had 2 episodes of jaundice and pruritus over a period of 4 years. The diagnosis criteria, clinical features, blood tests, etiopathogenesis and treatment are reviewed.

Antibodies to carbonic anhydrase and IgG4 levels in idiopathic chronic pancreatitis: relevance for diagnosis of autoimmune pancreatitis.

BACKGROUND: Increased serum antibodies against carbonic anhydrase II (CA-II Ab) or IgG4 levels have been reported in cases of autoimmune chronic pancreatitis (ACP). AIM: To assess the relevance of serum CA-II Ab and IgG4 levels for the diagnosis of ACP in idiopathic CP (ICP) versus alcoholic CP and Sjogren's syndrome (SS). SUBJECTS: This was a multicentre study involving 227 subjects divided into four groups: ICP (n = 54), normal controls (n = 54, paired by age and sex with ICP patients), alcoholic CP (n = 86), and SS (n = 33). METHODS: CA-II Ab was measured by ELISA and confirmed by western blotting. A score of easy clinical use with major clinical, morphological, and biochemical parameters for the diagnosis of ACP was applied. RESULTS: The percentage of patients with increased serum CA-II Ab was higher in the ICP group (28%) than in controls (1.9%) and in patients with alcoholic CP (10.5%), but lower than in patients with SS (64%). The proportion with elevated IgG4 levels was higher in the ICP group (15%) compared with controls (1.9%) and SS (0%) but not significantly different from alcoholic CP (8%). Most ICP patients (7/8) with high IgG4 levels exhibited increased CA-II Ab and a compatible ACP score. A definitive diagnosis of ACP by histological analysis was associated with other autoimmune disorders, an increase in both serum IgG4 and CA-II Ab levels, and IgG4 positive plasma cells. CONCLUSIONS: The increase in serum IgG4 levels was strongly associated with elevated CA-II Ab levels, manifestations compatible with ACP, and lymphoplasmacytic infiltration when surgical specimens were available.

Heparin mobilizes xanthine oxidase and induces lung inflammation in acute pancreatitis.

OBJECTIVE: To evaluate the effect of low molecular weight heparin on plasma xanthine oxidase concentrations and lung inflammatory response during acute pancreatitis. DESIGN: Randomized, controlled trial. SETTING: Experimental laboratory. SUBJECTS: Male Wistar rats. INTERVENTIONS: Acute pancreatitis was induced by intraductal administration of 5% sodium taurocholate. Low molecular weight heparin (0, 30, 90, or 300 units/kg) was administered immediately after induction of pancreatitis. MEASUREMENTS AND MAIN RESULTS: Lipase and xanthine oxidase plasma concentrations were measured 3 hrs after pancreatitis induction. Expression of P-selectin messenger RNA and myeloperoxidase activity as a marker of neutrophil infiltration were determined in the lung. An increase in xanthine oxidase plasma concentrations was observed during pancreatitis. Administration of heparin also increased plasma xanthine oxidase activity in both control and pancreatitis animals. Measures of xanthine oxidase present in the endothelial surface indicate that during pancreatitis, the enzyme is released from the gastrointestinal endothelium. By contrast, heparin mobilizes xanthine oxidase from almost all organs evaluated. Neutrophil infiltration was increased in the lung during pancreatitis. Heparin administration further increased, in a dose-dependent manner, myeloperoxidase activity and P-selectin expression in the lung in animals with pancreatitis. By contrast, in control animals, heparin had no effect on myeloperoxidase activity and did not induce P-selectin up-regulation. CONCLUSION: During acute pancreatitis, heparin administration might mobilize xanthine oxidase attached to endothelial cells, originating a free radical-generating system in the circulation that would trigger an inflammatory response in the lung.

Usefulness of alanine and aspartate aminotransferases in the diagnosis of microlithiasis in idiopathic acute pancreatitis.

CONCLUSION: Serum increases of aminotransferases, especially alanine aminotransferase (ALT), were suggestive of microlithiasis in idiopathic acute pancreatitis, particularly when assessed early after the onset of abdominal pain. BACKGROUND: It has been shown that biochemical laboratory values only are useful parameters in distinguishing gallstone from nongallstone acute pancreatitis. We assessed the diagnostic usefulness of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) for identification of occult microlithiasis in idiopathic acute pancreatitis. METHODS: Ninety-one patients with idiopathic acute pancreatitis who underwent microscopic examination of stimulated duodenal bile sediments were retrospectively studied. According to earliness of ALT and AST assay after the onset of abdominal pain, patients were divided into two groups: group A, within the first 24 h (n = 56) and group B, between 24 and 72 h (n = 35). RESULTS: ALT and AST values expressed as number of elevations of the upper limits of normal were higher in group A patients with positive biliary drainage than in group B. Median (range) ALT and AST values were 2.5 (0.1-18.1) vs 0.4 (0.1-8.6) and 3 (0.3-17.4) vs 0.5 (0.3-11.9), respectively. In the univariate analysis and receiver operating characteristic (ROC) curves, ALT within the first 24 h showed a sensitivity of 73%, specificity of 86%, and positive predictive value of 92% for a cutoff of 1.2 elevations of the upper limit of normal. These values were slightly higher, although without statistically significant differences, than those of AST (73, 80, and 89%, respectively).